Herpes simplex encephalitis

Alan C Jackson MD (

Dr. Jackson of Lake of the Woods District Hospital has no relevant financial relationships to disclose.

John E Greenlee MD, editor. (Dr. Greenlee of the University of Utah School of Medicine has no relevant financial relationships to disclose.)
Originally released August 16, 1995; last updated July 4, 2020; expires July 4, 2023


Herpes simplex virus infections are common and the virus is latent in ganglia in a large portion of the population. The virus may spread to the brain along a trigeminal or olfactory pathway and produce an encephalitis with characteristic localization in the temporal and frontal lobes. Early diagnosis and initiation of therapy with intravenous acyclovir are important in reducing the morbidity and mortality of herpes simplex encephalitis, so clinical suspicion must always be high for this disease. In this article, the author reviews the clinical features, pathogenesis, epidemiology, diagnosis, and management of herpes simplex encephalitis.

Key points


• Herpes simplex encephalitis is a sporadic encephalitis that often presents with focal neurologic symptoms and signs reflecting frontal and temporal lobe involvement.


• MR brain imaging and CSF studies (if no contraindications), including detection of herpes simplex virus DNA with polymerase chain reaction amplification, are important diagnostic investigations.


• Delays in initiation of intravenous acyclovir are associated with increased morbidity and mortality, with an untreated mortality rate of 70%.


• Intravenous acyclovir should be initiated as soon as possible on the basis of a clinical suspicion of herpes simplex encephalitis and continued for 14 to 21 days for confirmed disease or discontinued as soon as the diagnosis is excluded.

Historical note and terminology

Herpes simplex virus infections were described in ancient Greece. The term "herpes," which means to creep or crawl, was used to describe the spreading cutaneous lesions in the infections (Cumstom 1926). The Romans associated mouth and lip lesions with fever and used the term “herpes febrilis.” The ability of herpes simplex virus to travel from a peripheral site of inoculation to sensory ganglion cells and centrally into the CNS has been recognized since the early work of Goodpasture and Teague (Goodpasture and Teague 1923). Herpes simplex encephalitis was first reported in a 4-week-old infant in 1941 (Smith et al 1941) and, shortly afterward, in an adult patient (Zarafonetis et al 1944); intranuclear inclusions were demonstrated in brain tissue, and herpes simplex virus was isolated. Nahmias and Dowdle identified the 2 antigenic subtypes of herpes simplex virus (Nahmias and Dowdle 1968), which led to observations that herpes simplex virus-1 was primarily responsible for infections "above the belt,” whereas herpes simplex virus-2 was responsible for infections "below the belt." Over the past 30 years, there have been many advances in our understanding of herpes simplex virus and herpes simplex encephalitis. Herpes simplex encephalitis is a viral disease in which antiviral therapy has been demonstrated to have a dramatic beneficial effect on outcome.

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